Estrogen receptor beta activation prevents glucocorticoid receptor-dependent effects of the central nucleus of the amygdala on behavior and neuroendocrine function.
Estrogen receptor beta activation prevents glucocorticoid receptor-dependent effects of the central nucleus of the amygdala on behavior and neuroendocrine function.
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雌激素受体β激活可防止杏仁核中央核对行为和神经内分泌功能的糖皮质激素受体依赖性影响。
DOI：
10.1016/j.brainres.2010.03.098
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发表时间：
2010
期刊：
影响因子：
2.9
通讯作者：
Handa,RobertJ
中科院分区：
文献类型：
--
作者：
Weiser,MichaelJ;Foradori,ChadD;Handa,RobertJ
焦虑和抑郁等神经精神疾病具有巨大的经济和社会影响。下丘脑-垂体-肾上腺（HPA）轴的失调导致内源性糖皮质激素水平升高通常与此类病症相关。慢性高水平的糖皮质激素可能作用于杏仁核（CeA），将正常的适应性反应改变为适应不良和有害的反应。除了糖皮质激素，其他类固醇激素如雌二醇和雄激素也可以改变对威胁刺激的激素和行为反应。特别是，雌激素受体β（ERβ）激动剂已被证明具有抗焦虑作用。因此，这些实验提出了这样的假设，即选择性刺激CeA中的糖皮质激素受体（GR）会增加焦虑样行为和HPA轴对应激的反应性，并且进一步地，ERβ激动剂可以调节这些作用。将年轻成年雌性Sprague-Dawley大鼠卵巢切除，并通过立体定位手术将含有选择性GR激动剂RU 28362的蜡丸或空白丸双侧植入CeA背侧区域。4天后，给予动物ERβ激动剂S-DPN或溶媒（每天皮下注射4次）。使用高架十字迷宫（elevated plus maze，EMAZ）测量动物的迷宫型行为。中央RU 28362植入物引起显著更高的焦虑型行为，在ESTA和更高的血浆CORT水平比对照组给予空白中央植入物。此外，S-DPN治疗的动物，无论中央植入物的类型如何，都显示出比载体治疗的对照或植入RU 28362的载体治疗的动物显著更低的焦虑型行为和术后血浆CORT水平。这些结果表明，CeA内GR的选择性激活是致焦虑的，外周给予ERβ激动剂可以克服这种作用。这些数据表明，通过ERβ的雌二醇信号传导阻止了CeA对行为和神经内分泌功能的糖皮质激素依赖性作用。
Neuropsychiatric disorders such as anxiety and depression have formidable economic and societal impacts. A dysregulation of the hypothalamo–pituitary–adrenal (HPA) axis leading to elevated endogenous glucocorticoid levels is often associated with such disorders. Chronically high glucocorticoid levels may act upon the central nucleus of the amygdala (CeA) to alter normally adaptive responses into those that are maladaptive and detrimental. In addition to glucocorticoids, other steroid hormones such as estradiol and androgens can also modify hormonal and behavioral responses to threatening stimuli. In particular, estrogen receptor beta (ERβ) agonists have been shown to be anxiolytic. Consequently, these experiments addressed the hypothesis that the selective stimulation of glucocorticoid receptor (GR) in the CeA would increase anxiety-like behaviors and HPA axis reactivity to stress, and further, that an ERβ agonist could modulate these effects. Young adult female Sprague–Dawley rats were ovariectomized and bilaterally implanted via stereotaxic surgery with a wax pellet containing the selective GR agonist RU28362 or a blank pellet, to a region just dorsal to the CeA. Four days later, animals were administered the ERβ agonist S-DPN or vehicle (with four daily sc injections). Anxiety-type behaviors were measured using the elevated plus maze (EPM). Central RU28362 implants caused significantly higher anxiety-type behaviors in the EPM and greater plasma CORT levels than controls given a blank central implant. Moreover, S-DPN treated animals, regardless of type of central implant, displayed significantly lower anxiety-type behaviors and post-EPM plasma CORT levels than vehicle treated controls or vehicle treated animals implanted with RU28362. These results indicate that selective activation of GR within the CeA is anxiogenic, and peripheral administration of an ERβ agonist can overcome this effect. These data suggest that estradiol signaling via ERβ prevents glucocorticoid-dependent effects of the CeA on behavior and neuroendocrine function.